title: FasL expression on human nucleus pulposus cells contributes to the immune privilege of intervertebral disc by interacting with immunocytes.
abstract: The mechanisms of immune privilege in human nucleus pulposus (NP) remain unclear. Accumulating evidence indicates that Fas ligand (FasL) might play an important role in the immune privilege of the disc. We aimed for addressing the role of FasL expression in human intervertebral disc degeneration (IDD) and immune privilege in terms of the interaction between NP cells and immunocytes via the FasL-Fas machinery. We collected NP specimens from 20 patients with IDD as degenerative group and 8 normal cadaveric donors as control. FasL expression was detected by qRT-PCR, western blotting and flow cytometry (FCM). We also collected macrophages and CD8(+) T cells from the peripheral blood of patients with IDD for co-cultures with NP cells. And macrophages and CD8(+) T cells were harvested for apoptosis analysis by FCM after 2 days of co-cultures. We found that FasL expression in mRNA, protein and cellular resolutions demonstrated a significant decrease in degenerative group compared with normal control (p<0.05). FCM analysis found that human NP cells with increased FasL expression resulted in significantly increased apoptosis ratio of macrophages and CD8(+) T cells. Our study demonstrated that FasL expression tends to decrease in degenerated discs and FasL plays an important role in human disc immune privilege, which might provide a novel target for the treatment strategies for IDD.
authors.affiliation: Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 127 Changle Western Road, Xi'an, P. R. China.
authors.forename: Zhi-Heng
authors.initials: ZH
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Sun
authors.forename: Hai-Qiang
authors.initials: HQ
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ge
authors.forename: Ting-Shuai
authors.initials: TS
authors.lastname: Jiang
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Sheng
authors.initials: S
authors.lastname: Hu
authors.forename: Dino
authors.initials: D
authors.lastname: Samartzis
authors.forename: Zhuo-Jing
authors.initials: ZJ
authors.lastname: Luo
mesh_terms: D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007403:Intervertebral Disc / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein
keywords: CD8+ T cell.; FasL; immune privilege; intervertebral disc degeneration; macrophage